EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry

Abstract

Abstract Background Screening mutations in epidermal growth factor receptor (EGFR) to analyze non-small-cell lung cancer (NSCLC) profile is the criterion to choose the best therapeutic strategy. New Oncology guidelines recommend EGFR mutation analysis before prescribing tyrosine kinase inhibitors (TKIs) treatment. Majority of lung cancer patients are diagnosed at advanced stages and generally only small biopsies materials are available for diagnostic and molecular characterization. The aim of this first work is to screen EGFR mutation status in Tunisian NSCLC by mutation-specific immunohistochemistry (IHC) and molecular biology, to estimate the relevance of proposing TKIs as a new therapeutic line. Methods E746-A750 deletion and L858R mutations were screened in 50 unselected NSCLC formalin-fixed paraffin-embedded (FFPE) tissue samples. Mutation expression by IHC was evaluated by intensity and percentage of staining and correlated to patients’ data. DNA was extracted and EGFR mutations were analyzed by Sanger sequencing. Positive and negative controls were included for EGFR mutations in order to support the results. Results Among our patients (48 men and 2 women) all adenocarcinoma (confirmed by histology and IHC with TTF1/Napsin A), 94% were smokers exceeding the tobacco risk threshold (at least 25 pack-years) and the women were none. 44% had EGFR mutation by IHC: 26% had simple mutation and 18% had concurrent mutation. All mutated cases were smokers except a woman who was none. Concurrent mutations patients exceeded 40 pack-years. 91.4% of IHC results were validated by molecular analysis (100% of negative and 85% of positive cases) showing either T > G (exon 21) or 2235–2249 del (exon 19). Conclusions These preliminary results confirm the usefulness of IHC to detect EGFR mutations but the frequency of concurrent mutations doesn’t appear in favor of EGFR TKIs treatment. In fact, literature reports a significantly worse response compared to those with single mutation when treated by TKIs